ABSTRACT With the career goal of becoming an independent investigator, Dr. Marcus Bachhuber describes a mentored research project and a rigorous career development plan which will prepare him to study the implementation and testing of interventions to reduce morbidity and mortality from substance use. Prescriptions for opioid analgesics have increased dramatically and, in parallel, downstream consequences such as nonmedical use, opioid use disorders, and overdose have also increased. While most research focuses on opioid analgesics for chronic pain, the use of these medications for acute pain is also associated with a risk of adverse events such as overdose. Furthermore, up to three-quarters of people receiving an opioid analgesic prescription have leftover pills, which are often accidentally ingested (e.g., by children) or diverted for nonmedical use. Our project seeks to reduce harms from opioid analgesics used for acute non-cancer pain by reducing the quantity prescribed. The use of prescription defaults (i.e., a default number of pills for every new prescription) in the electronic health record (EHR) has the potential to change provider behavior, but has not been rigorously studied for opioid analgesics. This research centers on the implementation of default quantities for all new opioid analgesic prescriptions in the EHR, termed e-DROP (Electronic Defaults to Reduce Opioid Prescribing). In a cluster-randomized trial, we anticipate randomizing 27 primary care and 4 ED sites (over 900 providers writing in excess of 19,000 opioid analgesic prescriptions annually) to either e-DROP or the usual EHR. This proposal aims to: 1) Determine the impact of e-DROP on the quantity of opioid analgesics prescribed (primary outcome) as well as subsequent medication reorders and health care visits (secondary outcomes); 2) Examine the impact of e-DROP on patient-reported outcomes such as pain (primary outcome), leftover opioid analgesic pills, and satisfaction (secondary outcomes); 3) Determine provider factors associated with prescribing the default number of pills or fewer; and 4) Determine the effect of e-DROP on total direct health care costs. To accomplish these aims, Dr. Bachhuber will pursue training in implementation science, randomized controlled trial design and conduct, cost analysis of randomized trials, and advanced longitudinal data analysis. With completion of these activities, along with intensive mentorship, Dr. Bachhuber will develop the skills necessary to achieve his career goal of becoming an independent investigator.